Interferons are macromolecules, presumably glycoproteins, which are synthesized in a variety of vertebrate cells upon viral infection or some other stimuli. They are excreted, are bound to other cells and make these inefficient in supporting the replication of a broad range of viruses. They are, in general, species specific as far as the host is concerned. However, interferons produced in one cell species upon induction by any virus are active against all other interferon sensitive viruses in the same cell species. We have been studying the mode in which interferon treatment blocks the replication of viruses in interferon-treated cells. The major test systems in use include mouse L 929 cells, mouse Ehrlich ascites tumor cells, reovirus, and encephalomyocarditis virus. Studies in vivo are directed towards the comparison in control cells and interferon-treated cells of the accumulation of the various intermediates in virus replication. Most of these studies are performed with reovirus. The intermediates determined include the various single stranded reovirus RNAs, reovirus proteins, and double stranded reovirus RNAs. We are also testing the effect of interferon treatment on the accumulation, modification pattern and turnover of cellular ribonucleic acids and proteins. Various characteristics of extracts prepared from interferon- treated and control cells, are under investigation as well. The characteristics compared include the ability of the extracts to translate viral and cellular messenger RNAs. Similar studies are underway with various interferon sensitive human cell lines. BIBLIOGRAPHIC REFERENCES: Vassef, A., C. Spencer, T.D. Gelehrter and P. Lengyel: Selectivity of interferon action: Hormonal induction of tyrosine aminotransferase in rat hepatoma cells is much less sensitive to interferon than replication of vesicular stomatitis virus or reovirus. Biochem. Biophys. Acta 353, 115 (1974). Gupta, S.L., M.L. Sopori and P. Lengyel: Release of the inhibition of messenger RNA translation in extracts of interferon-treated Ehrlich ascites tumor cells by added transfer RNA. Biochem. Biophys. Res. Comm. 57, 763 (1974).